The present disclosure relates generally to the field of organic synthetic methodology for the preparation of Flaviviridae virus inhibitor compounds and their synthetic intermediates.
Viruses comprising the Flaviviridae family include at least three distinguishable genera including pestiviruses, Flaviviruses, and hepaciviruses (Calisher, et al., J. Gen. Virol., 1993, 70, 37-43). While pestiviruses, such as bovine viral diarrhea virus (BVDV), classical swine fever virus (CSFV, hog cholera) and border disease virus (BDV), cause many economically important animal diseases, their importance in human disease is less well characterized (Moennig, V., et al., Adv. Vir. Res. 1992, 48, 53-98). Flaviviruses are responsible for important human diseases such as dengue fever and yellow fever while hepaciviruses cause hepatitis C virus infections in humans. Other important viral infections caused by the Flaviviridae family include West Nile virus (WNV) Japanese encephalitis virus (JEV), tick-borne encephalitis virus, Junjin virus, Murray Valley encephalitis, St Louis enchaplitis, Omsk hemorrhagic fever virus and Zika virus.
Combined, infections from the Flaviviridae virus family cause significant mortality, morbidity and economic losses throughout the world. Although compounds with anti-Flaviviridae virus activity have been disclosed, none of these are currently clinically approved antiviral therapeutics. Therefore, there remains a need to develop effective treatments for Flaviviridae virus infections. Suitable compounds for the treatment of Flaviviridae virus infections are disclosed in WO 2011/088345, including the compound of Formula I as described herein.